What is the treatment for Clostridioides difficile (C. difficile) infection?

Treatment of Clostridioides difficile Infection (CDI)

For the treatment of Clostridioides difficile infection, oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) are strongly recommended as first-line therapies, with treatment selection based on disease severity. 1

Initial Treatment Based on Disease Severity

Non-Severe CDI

• Definition: WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1
• Recommended treatment:
  • Vancomycin 125 mg orally four times daily for 10 days, OR
  • Fidaxomicin 200 mg orally twice daily for 10 days, OR
  • Metronidazole 500 mg orally three times daily for 10 days (if access to vancomycin or fidaxomicin is limited) 1

Severe CDI

• Definition: WBC ≥15,000 cells/mL OR serum creatinine ≥1.5 mg/dL OR serum albumin <30 g/L 1
• Recommended treatment:
  • Vancomycin 125 mg orally four times daily for 10 days, OR
  • Fidaxomicin 200 mg orally twice daily for 10 days 1

Complicated/Fulminant CDI

• Definition: Hypotension, shock, ileus, or toxic megacolon 1
• Recommended treatment:
  • Vancomycin 500 mg orally four times daily, AND
  • Metronidazole 500 mg intravenously every 8 hours
  • If ileus is present: Add rectal vancomycin 500 mg in 100 mL normal saline as retention enema every 6 hours 1

When Oral Therapy Is Not Possible

• Non-severe CDI: Metronidazole 500 mg intravenously three times daily for 10 days 2
• Severe CDI:
  • Metronidazole 500 mg intravenously three times daily for 10 days, PLUS
  • Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or
  • Vancomycin 500 mg four times daily by nasogastric tube 2

Management of Recurrent CDI

First Recurrence

• If metronidazole was used for initial episode:
  • Vancomycin 125 mg orally four times daily for 10 days 1
• If standard vancomycin was used for initial episode:
  • Fidaxomicin 200 mg twice daily for 10 days 1

Second or Subsequent Recurrences

• Vancomycin in a tapered and pulsed regimen:
  • 125 mg four times daily for 10-14 days
  • 125 mg twice daily for 7 days
  • 125 mg once daily for 7 days
  • 125 mg every 2-3 days for 2-8 weeks 1, 3
• OR Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• OR Fidaxomicin 200 mg twice daily for 10 days 1
• OR Fecal microbiota transplantation (FMT) after appropriate antibiotic treatments for at least 2 recurrences 1, 2

Important Adjunctive Measures

1. Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1, 2
2. Avoid antiperistaltic agents and opiates, especially in the acute setting, as they may worsen symptoms 1, 2
3. Consider discontinuing proton pump inhibitors if not essential, though evidence for this is limited 2
4. Implement proper infection control measures:
   • Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores)
   • Contact precautions
   • Environmental cleaning and disinfection 2

Surgical Intervention

Consider surgical consultation for patients with:

• Perforation
• Systemic inflammation
• Toxic megacolon
• Severe ileus not responding to antibiotic therapy 1

Surgery is recommended before lactate levels exceed 5.0 mmol/L 1

Special Populations

Pediatric Patients

• Mild to moderate CDI: Metronidazole 7.5 mg/kg/dose three or four times daily for 10 days (maximum 500 mg per dose)
• Severe CDI: Vancomycin 10 mg/kg/dose four times daily for 10 days (maximum 125 mg per dose) with or without IV metronidazole 1

Emerging Therapies

• Bezlotoxumab: A monoclonal antibody that reduces CDI recurrence by blocking C. difficile toxin B, particularly useful in patients with CDI due to the 027 epidemic strain, immunocompromised patients, and patients with severe CDI 2, 4

Common Pitfalls to Avoid

1. Failing to discontinue the inciting antibiotic when possible
2. Using metronidazole for multiple recurrences (avoid due to potential neurotoxicity and hepatic toxicity) 3
3. Repeat testing within 7 days during the same episode of diarrhea (rarely changes management and may lead to false positive results) 1
4. Testing asymptomatic patients or those without clinically significant diarrhea (≥3 loose stools in 24 hours) 1
5. Delaying treatment in cases of high clinical suspicion while awaiting test results 1

By following these evidence-based guidelines for the management of C. difficile infection, clinicians can optimize treatment outcomes and minimize the risk of recurrence, which occurs in up to 25% of patients 5.